A large fraction of human breast tumors contain estrogen receptors and, thus, have the ability to concentrate estrogenic substances. In principle, one should be able to utilize this selective uptake mechanism to concentrate a gamma-emitting radiopharmaceutical whose distribution could be monitored by gamma-imaging techniques. Such a procedure would provide a unique, non-invasive diagnostic tool for localizing breast tumors and metastases and determining their receptor content. This project is concerned with the synthesis and evaluation of such receptor-based, selective breast tumor localizing agents. Halogenated derivatives (fluorine-18, bromine-77 and iodine-123) of various steroidal and non-steroidal estrogens will be prepared. The halogen will be placed at a position consistent with high chemical and metabolic stability and high receptor binding affinity, and the overall structure of the molecule will be designed to maximize its binding selectivity. This will be done by adjusting its structure to optimize its "merit factor", which is defined as the ratio of its binding affinity to the estrogen receptor to its binding affinity to non-receptor proteins. We have already prepared homologous series of iodostilbestrols and ring and side chain halogenated hexestrols; some of these compounds have merit factors in the 33-300 range. (The merit factor for estradiol is 100 by definition.) These compounds will be studied in vitro (receptor, serum, control and target tissue binding) and in vivo (tissue distribution and uptake selectivity) in animal model systems (DMBA-induced and R323OAC transplantable mammary tumor-bearing rats) to assess their feasibility as diagnostic agents for human breast cancer.